(a) Field of the invention
The present invention relates to 2-(4-pyridylaminomethyl)benzimidazole derivatives. These compounds exhibit antiviral activity. The compounds are particularly effective against enterovirus and rhinovirus which are the causative agents of several human diseases.
(b) Description of the prior art
Since the benzimidazole derivatives were reported to show antiviral activity by R. L. Thompson (The Journal of Immunology: Vol. 55, 345 (1947)), synthesis and biological evaluation of a large number of this series of compounds has been reported. Especially, 2-(anilinomethyl)benzimidazole represented by the following formula: ##STR2## has been reported in Chemical Abstracts (Vol. 59, 3906f), and has been shown to exhibit biological activity (Mizuno et al.; Yakugaku Zasshi: Vol. 85, 926-955 (1965)).
The present inventors also newly synthesized the series of 2-(4-pyridylaminomethyl)benzimidazole derivatives represented by the following formula: ##STR3## wherein n is 0, 1 or 2, R is lower alkyl, lower alkoxy, benzoyl, halogenomethyl, halogen, nitro or amino, their tautomers, and their acid addition salts, and these compounds were subjected to an antiviral activity test for primarily screening out promising ones (Japanese patent application No. 156,680/1985 dated July 15, 1985, which corresponds to U.S. patent application, Ser. No. 884,624 filed on July 11, 1986).
The picornaviruses are the causative agents of several disease states. Among the picornaviridae are two groups that cause disease in humans: the enteroviruses and the rhinoviruses. The enterovirus group consists of 68 distinct serotypes that have been associated with many diverse disease states, including poliomyelitis, neonatal sepsis, aseptic meningitis, pericarditis, myocarditis, hepatitis, eruption, acute hemorrhagic conjunctivitis and upper respiratory tract infections. Rhinoviruses have been shown to be important causative agents for the common cold. The widespread nature of picornavirus disease, the economic consequences, and impracticality of vaccine development have justified the search for chemotherapeutic agents.